Cats viremic with feline leukemia virus, subgroup C (FeLV-C) develop pure red cell aplasia (PRCA). This results from a block in BFU-E to CFU-E maturation. Although granulocytic and erythroid progenitors are infected, only erythroid differentiation is impaired. Thirty amino acids of variable region 1 (VR1) of the surface unit protein of the FeLV-C envelope are the genetic determinants of host cell infection, of retroviral interference, and of PRCA. We hypothesized that FeLV- C inhibits the cell surface expression (or function) of its receptor (via envelope-mediated interference), leading to PRCA. As a corollary, the receptor must have a critical role in normal erythropoiesis, but be redundant or non-essential for granulocytic differentiation. Using a retroviral vector cDNA library generated from cat (3201B) T cells, we have cloned the cDNA for the FeLV-C receptor (termed FLVCR). The predicted protein is comprised of 567 amino acids, has 12 membrane-spanning domains, and is likely a member of the major facilitator superfamily (MFS) of transporter proteins. There is significant homology with D-glucarate transporters in bacteria and C. elegans. The goals of this application are to study the physiology of FLVCR and to test our hypotheses. As D-glucarate (and other organic (sugar) anion) transport is not known to have any role in hematopoiesis, these studies should provide novel insights into the biology of early erythroid cell development, as well as the pathogenesis of PRCA.